Bone implants for the treatment of infection

ABSTRACT

Described herein are devices, systems and methods for treating disease and/or infection by the release of silver from an implant over an extended period of time. In particular, the devices described herein may be used to treat infections such as osteomyelitis by the controlled release of silver ions from multiple sites of an extended-use implant. This implant typically includes a plurality of arms that both anchor and help distribute the released ions within the tissue. Power may be applied to release the silver ions into the tissue.

CROSS REFERENCE TO RELATED APPLICATIONS

This patent application is a continuation of U.S. patent applicationSer. No. 16/015,085, filed Jun. 21, 2018, titled “BONE IMPLANTS FOR THETREATMENT OF INFECTION,” now U.S. Pat. No. 10,368,929, which is acontinuation of U.S. patent application Ser. No. 15/012,803, titled“BONE IMPLANTS FOR THE TREATMENT OF INFECTION,” filed Feb. 1, 2016, nowU.S. Pat. No. 10,004,548, which is a continuation of U.S. patentapplication Ser. No. 13/527,389, titled “BONE IMPLANTS FOR THE TREATMENTOF INFECTION,” filed Jun. 19, 2012, now U.S. Pat. No. 9,248,254, whichis a continuation of U.S. patent application Ser. No. 12/870,082, titled“BONE IMPLANTS FOR THE TREATMENT OF INFECTION,” filed Aug. 27, 2010, nowU.S. Pat. No. 8,221,396, which claims priority to the following U.S.provisional patent applications: Provisional Patent Application No.61/237,506, titled “SILVER ELLUTING BONE IMPLANTS AND METHODS OF USE,”filed on Aug. 27, 2009; Provisional Patent Application No. 61/340,587,titled “ANTIMICROBIAL ION ELUTING IMPLANTABLE DEVICE,” filed on Mar. 19,2010; and Provisional Patent Application No. 61/359,549, titled “SILVERELUTING BONE IMPLANTS AND METHODS OF USE,” filed on Jun. 29, 2010. Eachof these applications is herein incorporated by reference in itsentirety.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference in their entirety to the sameextent as if each individual publication or patent application wasspecifically and individually indicated to be incorporated by reference.

FIELD

The devices, systems and methods described herein relate generally tothe treatment of infection, and particularly to the treatment of boneinfections such as osetomyelitis using a bone implant that releasessilver ions.

BACKGROUND

Bone infections, such as osteomyelitis, can be debilitating or evenfatal, and are notoriously difficult to treat. For example,osteomyelitis is an acute or chronic bone infection that may be causedby bacteria or fungi. The infection that causes osteomyelitis may startin another part of the body and spread to the bone through the blood.The infection may also spread to a bone from infected skin, muscles, ortendons next to the bone, as in osteomyelitis that occurs under achronic skin ulcer (sore). Bone infection can also start after bonesurgery, especially if the surgery is done after an injury or if metalrods or plates are placed in the bone. In children, the long bones areusually affected. In adults, the feet, spine bones (vertebrae), and thehips (pelvis) are most commonly affected.

Treatment of osteomyelitis is typically intended to prevent theinfection from getting worse and ultimately to eliminate it from thebody. The currently accepted treatment for osteomyelitis requires anextended period of intravenous antibiotics. Antibiotics are given todestroy the bacteria causing the infection. More than one antibiotic maybe given at a time. The antibiotics are usually given intravenously, andmust be taken for at least 4-6 weeks, sometimes longer. In some cases,surgery may be required in order to remove dead bone tissue, and openspace left by the removed bone tissue may be filled with bone graft orpacking material that promotes the growth of new bone tissue. If anorthopedic prosthesis is present near the site of infection, treatmentmay also require surgical removal of the prosthesis and infected tissuesurrounding the area. A new prosthesis may be implanted in the sameoperation or delayed until the infection has gone away.

Chronic osteomyelitis may require amputation, especially in patientswith diabetes or poor blood circulation. Furthermore, osteomyelitis maybe particularly serious when it develops in patients having an implantor prosthesis. When bone becomes infected, pus produced within the bonemay result in an abscess that limits the bone's blood supply. The lostblood supply can result in chronic osteomyelitis. This chronic infectioncan cause symptoms, including pain and disability, which persist foryears.

Implants, and particularly silver-coated implants, have been suggestedfor use to control the spread of bacteria and the development ofinfection; however, such coatings have not proven effective. Silvercoatings have been typically too limited to treat infected regions thatare not immediately adjacent to the silver. In addition, the silver inmost coatings elutes far too slowly to repel or inhibit colonizingbacteria. Although more quickly-eluting silver coatings have beendescribed, such coatings typically do not last more than a few hours ordays, and are not sufficient for the longer-term treatment usuallyrequired to treat osteomyelitis and similar infections. In particular,previously described devices are not capable of delivering a sustainedlevel of silver ions to a large region of bone for a sufficient timeperiod.

U.S. Pat. No. 6,500,165 to Frank describes one variation of an activeantisepsis device that is intended to actively release silver from animplanted body site. However, this implant is limited by the deliverysurface, and is not readily anchorable into a tissue that is alreadynecrotic or damaged by infection, including infected bone tissue. US2006/00004431 to Fuller et al. describes a similar device, havingsimilar limitations.

Described below are implants that may address these problems and may beused to treat infections such as osteomyelitis. These devices may beimplanted over an extended period even in bone or other tissuestructures that are damaged or weakened by infection, and release silverions and/or other antimicrobial or therapeutic substances.

SUMMARY OF THE DISCLOSURE

Described herein are anti-microbial silver-releasing implants that maybe used to treat bone infections including osteomyelitis, as well asmethods of treating bone infections such as osteomyelitis using theseimplants.

In general, the devices described herein are implants configured forinsertion into a bone for an extended period of time (e.g., days, weeks,months, years, etc.). The bone implant may be anchored within the bone,and typically includes a plurality (e.g., 2 or more, 3 or more, 4 ormore, etc.) of arms that are extendable into the bone in a deployed oranchored (or deployed and anchored) configuration. Thus, in general,these implant may have a deployed configuration, in which the armsextend from the implant into the bone along different pathways throughthe bone, and a delivery configuration, in which the arms are retracted.In the retracted configuration, the implant may be linear or compact,simplifying the insertion into the bone. In some variations, the armsare individually extendable. In some variations the arms are connectedto each other and can be extended all together or in subsets.

The arms may be rigid, and may be configured for penetrating the bone,particularly the cancellous bone. For example, the arms may have a sharpor beveled edge. The arms may be formed of a material and/or shape tohave sufficient column strength for extending or pushing the arm intothe cancellous bone. In other variations, the arms are placed intopre-formed passages, and therefore have only nominal stiffness orrigidity (or column strength). The arms may be elongate members having atubular or flattened shape. In some variations the arms have a round,oval, rectangular, or other cross-section. In some variations the armsare formed of a metal (including alloys), plastic, ceramic or the like.In particular, the arms may be formed of a shape memory alloy such as anickel titanium alloy (e.g., Nitinol).

In general, each of the arms in the plurality of arms includes a sourceof silver. The source of silver may be referred to as a silverreservoir, and may be a solid silver material. The reservoir of silvermay be a silver plating or coating on all or a portion of each arm. Insome variations, the silver reservoir is a core of silver materialwithin an arm. At least one surface of the reservoir of a particular armmay be exposed along all or portion of the arm. In some variations,different arms include different silver reservoirs and different exposedopenings into the reservoirs.

As used herein an arm may include a wire (e.g., filament), a tube, aspike, a coil, etc. An arm is generally elongate and configured forextension from the implant when inserted into the bone (e.g., conversioninto the deployed configuration). An arm may be hollow or solid, and mayinclude one or more non-silver-releasing regions as well assilver-releasing regions. In some variations, the arm includesstructures that help anchor the arm (or the entire implant) within thebone. For example, the arm may include hooks, notches, prongs, or thelike. In some variations the arms include a deflection region that isdeflected to extend the arm from the implant when converting the implantinto the deployed configuration. The deflection region may be bent,curved, angled, or expanded from the typically more linear configurationof the arm in the delivery configuration. In some variations, the arm ispre-formed into a shape (including the deployed shape), and extendingthe arm from the implant during deployment into the bone allows thearm(s) to extend to their pre-formed shape. In some variations the armincludes a deflection ramp, notch or other structure to allow anotherarm to deflect during deployment, by moving against the adjacent arm.Examples of this are described in greater detail below.

The silver reservoir of each arm is typically connected to asilver-release driver that provide motivation to release silver ionsfrom the implant into the bone. The silver-release driver may be avoltage and/or current source, which may in turn be connected to controllogic that regulates the power applied (and therefore the silverrelease). In some variations the silver-release driver is a galvanicreactor metal (e.g., a metal that, when placed in contact with thesilver reservoir, drives the galvanic release of silver from theimplant).

For example, one variation of an implant as described herein, theimplant includes a guide body or structure (including a telescopingbody) from which two or more silver-releasing arms (in this example,filaments) may be controllably extended. The implant body and/or thefilaments are configured to be inserted into bone in a collapsedconfiguration in which the arms (filaments) are withdrawn into the guidebody. Once inserted within the bone, the filaments may be extended intothe bone. The implant may eventually (e.g., after days, weeks, months,etc.) be withdrawn from the bone by withdrawing the filaments back intothe guide body (or removing them completely). In some variations, theimplant guide body is left in position, and a new “core” region ofarms/filaments may be inserted in the same position, using the anchoredguide. Thus, the implant may be “recharged” to continue to releasesilver ions. In this example, one or more power sources may be connectedto the silver-releasing electrodes on the filaments and/or the body, sothat the silver may be actively released. Also described herein aremethods of using these devices and methods and devices for insertingand/or removing them.

As mentioned, some of the implants described herein include acurrent-controlled or voltage-controlled power source, including controlcircuitry, connectable to one or more silver-releasing arms (e.g.,wires, tubes, spikes, coils, etc.). The devices maybe configured tobranched delivery of ions (e.g., by including a plurality ofion-delivery elements that branch out to cover an area of tissue and/orbone). In some variations, the device may be galvanic or may includegalvanic release of ions in addition to active release. The current usedfor active release may be in the microamp range (e.g., between about 1microamp and about 50 microamps, between about 1 to about 30 microamps,between about 1.5 to 15 microamps, etc.).

For example, described herein are implants for insertion in to bone totreat infection, the implant having a collapsed insertion configurationand an expanded deployed configuration. The implant may include: aplurality of arms configured to extend from the implant in the deployedconfiguration, wherein each of the arms comprises a reservoir of silverconfigured to be released from the implant into the bone; an elongateand rigid guide comprising a plurality of deflection pathways, whereinthe plurality of arms are movably coupled to the elongate guide so thatthey may be extended from the deflection pathways and deployed todifferent bone regions to convert the implant from the collapsedinsertion configuration into the expanded deployed configuration; and asilver-release driver coupled to the reservoirs of silver to driverelease of silver ions from each of the plurality of arms.

In some variations, the implant further includes a bone anchorconfigured to secure the implant at least partially within a bone. Thebone anchor may be coupled to (or integral with) the elongate guidebody. For example, the anchor may include one or more fastening orattachment sites for sutures, screws or the like. An anchor may includea projecting element (e.g., prong, etc.) that secured into the bone.

The elongate guide may be an elongate hollow member within which thearms are contained so that they can be extended for deployment. In somevariations, the guide is a solid member to which the arms are secured.For example, the guide may include a core member around which the armsare slideably arranged. The guide may include channels, ramps,deflection regions, or the like for guiding each or the arms duringdeployment (or retrieval). During deployment the distal ends of the armstypically move from the central axis of the implant into an expandedconfiguration out of the implant.

The deflection pathways of the elongate guide may include openings,e.g., windows, along the long axis of the elongate hollow member. Armsmay exit these windows to expand into the bone during deployment.

For example, an elongate guide may include an elongate inner memberhaving a longitudinal axis and a deflection ramp region forming theplurality of deflection pathways that are configured to deflect the armsfrom longitudinal axis as they are extended into the deployedconfiguration.

As mentioned above, the plurality of arms may be formed of anyappropriate material, including a shape-memory material. For example, insome variations, the arms may comprise a nickel titanium alloy (e.g.,Nitinol) covered by a non-reactive (e.g., passivation) layer beneath asilver coating, wherein the non-reactive layer is formed directly ontothe nickel titanium material, after removal (or before formation) of atitanium oxide layer from the outer surface of the nickel titaniumalloy. The non-reactive layer may be an adhesion layer that enhances theadhesion of silver to the shape-memory material. Typically nickeltitanium will form an oxide layer on the outer surface. However, thisoxide layer may prevent the material from easily bonding to the silvercoating or silver reservoir. Thus a non-reactive layer (e.g., gold,etc.) may be used to both help adhere the silver to the nickel titanium,and to prevent leeching of nickel from the alloy.

The arms may be bent and/or curved when extended in the deployedconfiguration. As mentioned, the arms may comprise tissue-penetratingends. In general, the arms are configured to expand within cancellousbone during insertion of the implant. In some variations, the pluralityof arms are distributed asymmetrically about the radius of the elongateguide in the insertion configuration.

The plurality of arms may include arms of different lengths, and shapes.The silver reservoirs may be differently positioned and configured oneach arm or groups of arms. Typically, the implants described herein mayhave the arms arranged so that, when the arms are in the expandedconfiguration, they form a space-filling structure from which silver maybe released to cover a predetermined bone region. Thus, the arms may beexpanded into different directions and orientations. The arms may bearranged symmetrically or asymmetrically when expanded into the deployedconfiguration.

The plurality of arms may be configured to release silver along theirentire expanded length, or from a plurality of discrete locations alongtheir length. As mentioned, the reservoir of silver may be a silvercoating, and/or a silver core.

Also described herein are delivery devices for use with the implantsdescribed herein. A delivery device may be adapted to allow insertionand expansion of the implant while in the bone. In some variations thedelivery devices may also be configured to allow removal/retrieval ofthe implant. The delivery device may be used to remove the entireimplant or just a portion of the implant, such as the arms, for example,when reloading or recharging the implant with new silver-releasing arms.In some variations the delivery device may be used to remove and replacethe silver-release driver or a component of the driver (e.g. battery).

For example, in some variations the implant includes a delivery devicecoupling region at a proximal end of the elongate guide, wherein thecoupling region is configured to couple the implant to a delivery deviceso that the plurality of arms may be expanded or retracted relative tothe elongate guide. The coupling region may be a threaded region, forexample. Any appropriate coupling regions may be used. The implant mayinclude a first delivery device coupling region at a proximal end of theelongate guide and a second delivery device coupling region coupled to aproximal end of the plurality of arms, wherein the first delivery devicecoupling region and the second delivery device coupling region are eachconfigured to couple the implant to a delivery device so that theplurality of arms may be expanded or retracted relative to the elongateguide.

As mentioned, above, the silver-release driver may comprise a battery.In some variations the silver-release driver comprises logic configuredto provide pulsatile stimulation to drive release of the silver ions.

Also described herein are implants for insertion into a bone to treatinfection, the implant having an expanded deployed configurationconfigured for long-term release of silver ions and a collapsedinsertion configuration. The implant may comprise: an elongate outerhousing having a plurality of channel windows along the length of theelongate body; an inner treatment member comprising a plurality ofradially-expandable arms configured to extend from the channel windowsof the elongate outer body; wherein each of the radially-expandable armscomprises a silver reservoir, and wherein the inner treatment member isaxially slideable relative to the outer housing to expand the pluralityof radially-expandable arms from the collapsed to the deployedconfiguration; and a silver-release driver coupled to the reservoirs ofsilver to drive release of silver ions from each of the plurality ofarms.

As mentioned, in some variations the plurality of radially-expandablearms are coated with silver. The plurality of radially-expandable armsmay be formed of a material having sufficient stiffness to allow thearms to penetrate the target bone region when extended from the channelwindows.

The inner treatment member (or a portion of it) may be formed of anickel titanium alloy. In some variations, the distal tips of the armscomprise chisel-shaped tissue-penetrating distal tips.

The implant may also include a first applicator coupling region on aproximal end of the outer housing and a second applicator couplingregion on the proximal end of the inner treatment member, wherein thecoupling regions are configured to couple the implant to a deliverydevice so that the plurality of arms of the inner treatment member maybe expanded or retracted relative to the outer housing.

Also described herein are implants for insertion into a bone to treatinfection, the implant having an expanded deployed configurationconfigured for long-term release of silver ions. The implant mayinclude: a plurality of deflection arms having a first axially elongateddelivery configuration and a second radially deflected deliveryconfiguration, wherein each of the deflection arms comprises a silverreservoir, and wherein the deflection arms are further configured toslide axially relative to the other deflection arms to convert thedeflection arm from the delivery configuration into the deliveryconfiguration; further wherein the plurality o deflection arms areadjacent to each other; a deflection ramp on each deflection armconfigured to convert an adjacent deflection arm from the deliveryconfiguration to the deployed configuration as the adjacent deflectionarm is moved axially against the deflection ramp; and a silver-releasedriver coupled to the reservoirs of silver to drive release of silverions from each of the plurality of deflection arms.

Also described herein are systems for treating osteomyelitis byinserting an implant configured for the long-term release of silver ionsover a region of bone. A system may include a silver-releasing implant(including any of the implants described herein) and a delivery device.For example, the system may include a silver-releasing implantincluding: a silver-releasing implant having a collapsed insertionconfiguration and an expanded deployed configuration, the implantcomprising: a plurality of arms configured to extend from the implant,wherein each of the arms comprises a reservoir of silver configured tobe released from the implant into the bone; an elongate guide forming aplurality of deflection pathways for the arms, wherein the plurality ofarms are movably coupled to the elongate guide so that the arms may beextended from the elongate guide at different locations and orientationswhen the implant is converted to the deployed configuration; a firstcoupling member on a proximal end of the elongate guide configured forreleasably coupling to a delivery device; and a silver-release drivercoupled to the reservoirs of silver to drive release of silver ions fromeach of the arms.

A delivery device may include an elongate insertion member having adistal coupling region configured to releasably couple with the firstcoupling member; and an arm-extender member configured to couple withand extend the arms of the implant; and a handle at a proximal end ofthe delivery device.

In some variations, the system includes a control on the distal endconfigured to control extension/retraction of the arms of the implant.The arm-extender of the delivery device may include a coupling region atthe distal end configured to releasably couple with a coupler on theplurality of arms. The arm-extender may be a push rod. In somevariations, the arm-extender is slideably disposed within the elongateinsertion member for extending or retracting the arms. The arm-extendermay be configured to separately engage one or a subset of the pluralityof arms and to separately control extension or retraction of the one ora subset of arms.

Also describe herein are methods of treating infection in a bone, themethod comprising: inserting a silver-releasing implant into a bone in acollapsed configuration; expanding a plurality of arms from the implantinto the bone from the collapsed configuration into an expandedconfiguration wherein the expanded arms extend in a pattern havingmultiple pathways through the bone; releasing silver ions from one ormore silver reservoirs on the arms into the bone over an extended periodof time at a sustained level; and removing the implant after apredetermined period of time that is longer than a week.

The step of inserting may comprise forming passageways (passages) forthe implant and the expanded arms (e.g., before insertion of theimplant). A device for forming the passageways may be used. This devicemay be referred to as an implant template or as a passage formingimplant or device. The implant template may have an expandedconfiguration shape that is similar to that of the implant. For example,the implant template device may have a plurality of projecting “arms”that are configured to be inserted into the bone and form passages forthe insertion of the implant. In some variations the implant templateand/or the arms of the implant template are configured to cut, compress,carve, ablated, or otherwise form channels in the bone into which theimplant and the implant arms of the implant can be inserted. Forexample, the template device may include arms that are rigid, hard,sharp, stiff, or otherwise tissue-penetrating. The arms of the templatedevice may be extendable or expandable. In some variations, the templatedevice is anchored to the bone so that one or more components can bedriven into or through the bone to form the arm passageways. A centralpassageway may be formed first by drilling or other means, and apassageway forming device can then be inserted into the centralpassageway to form the passages for the arms of the treatment implant.For example, the step of inserting may comprise inserting a passageforming implant having a plurality of expandable members to pre-form thepassageways. Thereafter an implant having a plurality ofsilver-releasing arms may be inserted into the pre-formed passageways.The pre-formed passageways may be large enough to accommodate thetreatment implant, or they may act as “pilot” holes or guides throughthe bone, so that the implant arms themselves still penetrate thetissue, ensuring a tight apposition between the implant and the bone. Insome variations the treatment implant has arms that are of relativelylow column strength, and benefit from the use of pre-formed passageways.

In some variations, the method includes the step of driving the arms ofthe implant through the bone by extending the arms from the implant,wherein the arms are sufficiently stiff and/or sharp to penetrate bone.

The method may also include the step of anchoring the implant in thebone. The implant may be anchored before extension/expansion of thearms, or it may be anchored after extension of the arms. Extending thearms into the delivery configuration may help to anchor the implant inposition. In some variations the implant includes a guide or referenceregion, such as a core region or an elongate outer housing, againstwhich the implant arms move to expand into the deployed configuration;this guide or reference region may be anchored, and may include anchorscoupled thereto, as mentioned above.

The step of releasing silver ions may comprise applying energy to drivethe release of ions. For example, the method may include applying lessthan 50 microAmps of power to release ions. The step of releasing silverions may comprise applying pulsatile energy to release ions. The step ofreleasing silver ions may comprise applying pulses of energy to maintainthe silver ion concentration above a minimum inhibitory concentration.

In general, the step of releasing silver ions may include releasingsilver ions to maintain the silver ion concentration above a minimuminhibitor concentration in a predetermined region of bone surroundingthe implant for a predetermined period of time. The minimum inhibitorconcentration is typically the concentration of silver ions necessary totreat infection by killing microorganisms and inhibiting microbialgrowth. For example, the minimum inhibitory concentration may be betweenabout 0.01 microgram/ml and about 10 microgram/ml (e.g., between 0.1microgram/ml and about 1 microgram/ml). Any appropriate predeterminedtime period may be selected, including, for example, about 1 week, 1month, 2 months, 3 months, 6 months, 1 year, 2 years, etc. (includingany time period between 1 week and five years). The implant may beconfigured to provide the minimum concentration for the predeterminedtime period based on the power requirements and the silver-releasedriver (e.g., battery). The region of the bone surrounding the implantis typically a region extending from about a few mm to many cm aroundthe arms of the implant. The arms of the implant may be configured sothat the effective range of silver ion elevation to the minimumeffective concentration from the various arms overlaps, are adjacent, orare additive in the overlapping regions between adjacent arms. Thus, theimplants described herein having multiple arms may provide an enlargedregion of elevated silver (compared to implants that do not havemultiple arms) even at lower power requirements.

As mentioned, the arms of the implant may be extended by extending themfrom a guide region and/or by moving the arms relatively to each other(e.g., over or against each other). A delivery device may be used tofacilitate the expansion of the arms into the bone. In some variations,the step of inserting comprises inserting the implant with a deliverydevice configured to hold one region of the implant while longitudinallymoving another region of the implant to extend the arms.

After insertion, the silver-releasing (treatment) implant may be removedusing an inserter. For example, the implant may be removed with adelivery device configured to secure a proximal region of the implantwhile longitudinally moving another region of the implant to contractthe arms. All or just a portion of the implant may be removed. Forexample, the arms of the implant may be removed so as to insert a freshsilver reservoir for release. The new implant arms may be inserted intothe spaces in the one left by the previous arms, or into new boneregions. In some variations, the silver-release drive may be replaced inthis manner, leaving the rest of the implant in position. Alternatively,the arms may be left in position and the rest of the implant (e.g., anycore or guide region) may be removed or replaced. In some variations,the entire implant may be removed or replaced.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is one variation of an anti-microbial silver-releasing implant,as described herein.

FIG. 1B is an exploded view of the implant of FIG. 1A.

FIG. 2A shows the battery, arm housing and arms of the device of FIGS.1A and 1B.

FIG. 2B shows the distal end region of the housing from which the armsmay extend.

FIG. 3 shows another variation of a set of arms.

FIG. 4A shows one variation of an arm.

FIG. 4B shows another variation of an arm.

FIGS. 5A and 5B illustrate one variation of an implant in which thesilver-releasing arms are retracted (FIG. 5A) and extended (FIG. 5B).

FIG. 6 illustrates one variation of the implant described herein inwhich the silver-releasing arms are releasing silver into thesurrounding tissue.

FIG. 7 illustrates a region of bone (tibia) exhibiting osteomyelitis.

FIGS. 8A-8C illustrate insertion of an implant as described herein intothe bone using a telescoping inserter.

FIG. 9 shows another variation of an implant.

FIGS. 10A-10C illustrate the implant of FIG. 9; FIG. 10C illustrates theimplant inserted into a rabbit femur.

FIG. 11A illustrates the effect of an implant that uses galvanic releaseof ions.

FIGS. 11B and 11C illustrate one variation of the galvanic release ofsilver ions which may be used in an implant as described herein.

FIGS. 12A-12D illustrate another variation of an implant for releasingan antimicrobial ion.

FIGS. 13A-13E show another variation of a system including asilver-releasing implant for insertion into a bone to treat infection.

FIGS. 14A-14D illustrate another variation of a system including asilver-releasing implant for insertion into a bone to treat infection.

FIGS. 15A-15C show another variation of a system including asilver-releasing implant for insertion into a bone to treat infection.

FIGS. 16A-16C show another variation of a silver-releasing implant forinsertion into a bone to treat infection.

FIG. 17 shows one variation of an arm including a pair of bone-samplingregions.

FIG. 18 shows one variation of an implant including bone-samplingregions.

FIGS. 19A-19E illustrates one variation of a system including asilver-releasing implant for insertion into a bone to treat infection.

FIGS. 19F-19J illustrate insertion of the implant shown in FIG. 19A.

FIGS. 19K and 19L illustrate various methods for removing the implant ofFIG. 19A.

FIGS. 20A and 20B illustrate another variation of a silver-releasingimplant for insertion into a bone to treat infection.

FIGS. 21A and 21B illustrate another variation of a silver-releasingimplant for insertion into a bone to treat infection.

FIG. 21C shows a cross-section through the implant of FIG. 21A.

FIG. 21D shows an alternative variation of the implant of FIG. 21A.

FIGS. 22A and 22B illustrate another variation of a silver-releasingimplant for insertion into a bone to treat infection and aninsertion/activation device.

FIG. 23 illustrates one variation of an implant inserter and remover.

FIGS. 24A-24E illustrate removal of one variation of a silver-releasingimplant, as described herein.

FIG. 25 shows one variation of a coupling region that may be used as aconnector.

FIGS. 26A and 26B illustrate another coupling structure and method ofcoupling.

FIGS. 27A and 27B illustrates the coupling means shown in FIGS. 26A and26B expanding an inner member within a surrounding outer member.

FIGS. 28A and 28B illustrate another coupling structure and method ofcoupling.

FIGS. 29A-29D show one variation of a silver-releasing arm.

FIGS. 30A and 30B illustrate another variation of a silver-releasingimplant as described herein.

FIGS. 31A and 31B show another variation of a silver-releasing arm.

FIG. 31C illustrates another variation of silver-releasing implantsdeployed in a bone region.

FIGS. 32A and 32B illustrate another variation of a silver-releasingimplant for implantation into a bone.

DETAILED DESCRIPTION

Described herein are devices, systems and methods for treating boneinfection by the active release of an antimicrobial (e.g., silver ions)from an implant. In particular, the devices described herein may be usedto infections such as osteomyelitis by the controlled release of silverions from multiple sites of an extended-use implant. The implant istypically configured to be implanted into bone for an extended period oftime (e.g., days, weeks, months, or even longer) and to release silverions (and in some embodiments other medicaments). In these variations,active release of silver ions may lead to greater tissue concentrations,and thereby have an enhanced bactericidal or therapeutic effect comparedto passive (e.g., diffusion) of ions or medicaments.

In some variations of the devices described herein, the implant includesan implantable body from which one or more (often a plurality) ofsilver-releasing arms (e.g., filaments, plates, wires, branches, etc.)may be extended into the tissue. In particular, the implant may includea guide body having a plurality of silver-releasing arms. The arms aretypically extendable from the guide body. The guide body may steer ordirect the arms as they are extended from the body, and/or maycoordinate the expansion of the arms. The guide body may be an outermember (e.g., a hollow cannula member) out of which the arms extend, orit may be an inner core member against which the arms slide, or somecombination thereof. The guide body may include a plurality of channels,openings, deflection ramps, or other guide elements for engaging andguiding the arms. The arms typically slide against (relative to) theguide body. The guide body may be rigid. The guide body is typicallyelongate (e.g., having a longer length than width) and may have anyappropriate cross-section, e.g., round, oval, flat, square, etc.

The arms may be configured to penetrate the bone upon leaving the guidebody. For example, the arms maybe reinforced with a durable metalsubstrate such as a shape memory alloy (e.g., nickel titanium). Thesearms may be coated, filled, embedded or may otherwise carry a source ofsilver ions that is in communication with one or more silver-releasedrivers. In some variations, the silver reservoirs coupled to thesilver-release driver by one or more electrical contacts (e.g., an anode(+)); the implant guide body may also includes one or more returncontacts (e.g., cathodes (−)) which may be located anywhere on theimplant, spaced apart from the cathode, so that silver ions may bereleased from the implant into the bone or other surrounding tissue. Forexample, the return contact(s) may be on a different portion of thefilament, on another filament, or on the body of the implant.

The body of the device may be configured to penetrate the bone, and mayhave a tapered distal end and/or tip. In some variations, the distal endof the implant includes bone-engaging members (e.g., teeth, grips,threads, etc.) for securing the implant into the bone; in othervariations the distal end of the implant is substantially smooth so thatthe implant is engaged within the bone by the filaments.

As mentioned, the arms may be extendable and/or retractable from thebody of the implant. In some variations, one or more ports, windows, oropenings on the guide body region may permit extension of the filamentsfrom the device. The arms maybe extended by advancing out of the body.Thus, the implant may include a delivery configuration in which the oneor more arms are retracted within the guide body, and an implantedconfiguration in which the one or more arms are extended from the body(e.g., out of a port or ports on the body). In some configurations thearms are partially retracted into the body in the deliveryconfiguration, or be flush with the surface of the body. In somevariations the arms are retractable back within the body of the implant(e.g., for removal or repositioning of the device). In some variationsthe arms may be extended gradually or incrementally. For example, as theimplant is operated and silver is released from one or more regions ofthe arms, additional arms (or completely new arms) may be extended fromthe guide body with additional sources of silver.

Any appropriate arm that may contain or support a source of silver ionsfor active release may be used. For example, arms may be solid orhollow. Further, the source of silver ions may be applied to the outsideof all or a portion of the arm (e.g., by a coating), or it may becontained within the wall of the filament, or within a core region ofthe arm. In some variations, the arm is filled with the releasablesilver. Hollow arms may be particularly useful for co-delivery of otheragents such as medicaments in addition to the delivery of silver ions(e.g., antibiotics, bone growth promoting agents, etc.). Thus, the armsmay include a lumen or passageway through which material may bereleased.

The arms may be configured to penetrate tissue, and in particular, theymay be configured to penetrate bone. For example, the arms may bereinforced, or may include a relatively stiff material such a metalhaving a sufficient strength and durability. The distal end of the armmay be tissue penetrating (e.g., sharp). The arm may be any appropriatesize. For example an arm may have a diameter of between about 0.05 mmand about 5 mm. The diameter of the arm may be constant, or it may varyalong the length of the filament (e.g., it may taper distally). Animplant may have arms of different configurations (including lengths,shapes, materials, silver reservoirs, etc.).

Arms may be pre-based to assume a shape when extended from the body ofthe device. For example, when arms are formed of nickel titanium orother shape-memory materials, the arm may be configured to extend awayfrom the body of the device. The exit port for the arm from the body ofthe device may include a deflecting surface to direct the arm in adesired location away from the body as it is extended. In variationshaving more than one arm extendable from the body, the arms may beextended independently or as a group or plurality of groups.

Any of the devices described herein may also include one or moresensors. For example, a pH sensor may be associated with the body of thedevice for sensing pH in the surrounding of the bone. pH may be oneindicator of bacterial load, and the power or frequency of silverrelease may be modified based on the pH reading. Other sensor mayinclude silver sensors (which may be used to regulate the release).Internal sensors may also be provided. For example, a sensor or detectormay be included to monitor or otherwise indicate the level of power inthe implant, and/or the level of silver. Information from thesesensor(s) may be used by a controller to modify the activity of thedevice (e.g., increasing/decreasing the release of silver), and/or itmay be communicated outside of the patient's body, via a wired orwireless connection.

The active silver-release devices described herein may include anon-board power source (e.g., a battery, inductive coil, etc.) forapplying current to release the silver. When a battery is used, thesilver source in placed in electrical contact with the battery and thereturn electrode (e.g., cathode) is also placed in electrical contactwith the battery. As mentioned the silver source (and anode) may bepresent on the arms and the return electrode (cathode) may be present inone or more locations on the body, arm(s) or elsewhere on the device, sothat the silver can be released in a desired pattern from the implantwhen in a subject's body (e.g., within the bone). As mentioned, thedevice may also include a control or controls (e.g., circuitry) forcontrolling the applied power (e.g., current and/or voltage), for timingthe active powering of the device, and/or for controlling, communicationor monitoring with any sensors on the device, or any telemetryassociated with the device.

In operation, the device may be controlled so that silver is releasedcontinuously or intermittently (in pulses), or based on somepre-determined schedule (e.g., initially higher, or for a longer period,which gradually tapers off). For example, if power is applied by acurrent or voltage source, power may be applied continuously or inpulses or bursts of pulses. Alternatively, the device may be activelycontrolled, as mentioned above, so that power is applied based onfeedback from the tissue or implant. In some variations, the deviceapplies power to release silver intermittently, for some on-period,followed by a quiescent period (off-time). During the application ofpower (e.g., current), the power applied may be continuous or variable.The power may be pulsed (e.g., at some frequency) to help with releaseof the ions. The current may be applied at any appropriate level. Forexample, the applied current may be less than 10 mA (e.g., less than 1.0mA, less than 0.5 mA, etc.). The applied current may depend upon theapparent load of the device (e.g., depending on where in the body—or inthe bone—the implant is positioned).

The power source for an implant may be voltage-regulated or currentregulated, which may also be referred to as voltage controlled orcurrent controlled. For example, the system may be configured tomaintain a target current or a target voltage. A current controlled orvoltage controlled system may be used to achieve a constantcurrent/voltage, or when the voltage or current is controlled to bevarying (e.g., ramped, pulsed, etc.). The constant current may put out(cause the release of) the same amount of silver, and may adjust thevoltage to maintain the target (e.g., constant or relatively constant)current. The device may be limited to prevent excessive voltages. Thecurrent controlled embodiments may drive the ion-releasing reaction at aknown or predetermined rate. In voltage controlled embodiments, thedevice may keep the concentration of the silver relatively constant,regardless of the rate of release. This variation may allow the currentto vary to achieve a target (e.g., constant) voltage.

In general, the current range for a constant-current configuration maybe in the sub-microamp (e.g., nanoamp), microamp, or milliamp range(e.g., approximately 1.5 μA to 15 μA). Although the device may applycurrent in the milliamps range, this may be unnecessary in order toprovide sufficient concentration of ions to have the desired effect. Forexample, a high-current embodiment may result in an unnecessarily highconcentration. In some variations, the applied current is an extremelylow current (e.g., in the order of microamps or nanoamps). For example,the current may be between about 1 microamp and 50 microamps. Forexample, the current applied by the device (constant or varying) may beapproximately 1 microamp, 1.5 microamps, 2 microamps, 3 microamps, 4microamps, 5 microamps, 10 microamps, 15 microamps, 20 microamps, 30microamps, 40 microamps, 50 microamps, or any value between these).

In some variations the implant is inserted using a telescoping deliverydevice (e.g., cannula), or the body of the implant is itselftelescoping. Telescoping implants may be configured to maximize orincrease the tissue/therapeutic interface. In addition, the telescopingimplants allow for serial dilation through necrosed or infected bone tohealthy bone providing a more stable implant anchor that is fullyremovable upon therapy completion.

RELEASE OF IONS

As described herein the method of release of silver (or any other ion,particularly antimicrobial ions) may be through an electroporation-likerelease. A source of silver ions (e.g., silver, silver-ion dopedmaterials, etc.) may be placed in electrical communication with a firstelectrode (e.g., an anode (+)). A single arm may have one or more suchelectrodes and/or sources of silver ions. A return electrode (orplurality of return electrodes (e.g., cathode (−)) may be placed somedistance from the first electrode(s), so that when power is appliedacross these first electrode(s) and the return electrodes, ions arereleased to travel into the body by the flow of current.

The arm structures described herein may be expanding structures thatboth penetrate and anchor the implant into the tissue, and alsoestablish a broad distribution pattern for the ion distribution. Thesearms (which may be a stiff, non-eroding material such as Nitinol) maystabilize the implant even in necrotic bone or other tissues and befully retractable upon completion of therapy.

Although many of the variations described herein are powered by on-boardpower sources (e.g., battery, induction coil, etc.), they may also bepowered by an off-board power source, and may include a cable or wireconnection. For example, in some variations, the devices may be placedor positioned by guidewire. The guidewire may also be used to providepower to the device (thus the guidewire may be otherwise insulated).

In any of the variations described herein the device may include one ormore on-board controllers, and may be controlled automatically,programmed, or may receive input from one or more sensors orcommunication sources (e.g., wireless communication) that may controlone or more aspects of the device (including the time on/timeoff/frequency of current applied/level of current applied/voltageapplied/etc.). The power source may be internalized (within theimplant), and could use external control (e.g., an external magneticfield) to activate/deactivate. In some variations, communication orcontrol may be via RF communication.

Thus, in any of these variations, the device may be anchored into thebone, at or near an infection site, or prophylactically near a site thatis prone for infection (e.g., near another implant or orthopedicdevice). The implant may be configured to expand upon insertion so thatthe arms are separated from the return electrode(s) in a patternsufficient to apply silver ions to the infection region at the desiredeffective level.

In some variations the creation and release of the ions (e.g., silverions) may be galvanic or may be galvanic in addition to the active(powered) techniques described above. For example, germicidal ions maybe generated by coupling a metal with antimicrobial ions properties(such as silver or zinc) with another metal to form a galvanic cell. Forexample, a silver wire, plating, or film (either mechanical deposited orchemical deposited) or a material having silver as a component of analloy, may be placed in contact with another metal or alloy in form of awire, plating, film or a component of an alloy, to create a galvaniccell that creates and releases germicidal ions such as Pt, Pd, Au, etc.In one variation, the device includes one or more Nitinol supports(e.g., wires) having a silver coating connected to a conductivecomponent (stainless steel or Nitinol) with Pt, Pd or gold coating.

FIG. 11A illustrates the efficacy of galvanically generated silver ionsin preventing bacterial growth (1101 clear zones in the figure). In thisexample, silver wire has been wrapped with another metal (e.g., Pt) tocreate a galvanic response that causes the release of silver ions. Thereleased silver ion results demonstrated that bacteria were killed andbacterial growth inhibited in a cleared area around the growingbacterial colonies.

FIG. 11B shows a schematic of the galvanic action resulting in silverrelease. In this example, the silver material 1107 (e.g., a reservoir ofsilver on an arm) is placed in electrical contact with a galvanicreactor metal 1109. The two materials may be surrounded by thecancellous bone and any ionic and/or conductive material (e.g., saline,blood, cellular matrix, etc.) therein. In general, the galvanic reactormetal 1109 in this example is typically a more noble metal or alloy thansilver (e.g., platinum). This contact (in the conductive medium) mayresult in an oxidation-reduction reaction, leading to the release ofsilver ions by the galvanic reaction. This is shown in FIG. 11C,resulting in a region surrounding the metals (within the bone, forexample) of increased silver ions by the release 1111. The releasedsilver 1113 may diffuse or be actively driven from the cathode (silver1107) into the surrounding bone.

In some variations the galvanic activity/release is aided or assisted byactive (electrical) source.

Any of the treatment devices described herein may also be retrievable.For example, the extended arms may be retracted to remove the device. Insome variations, the body of the device is telescoping, so that it canbe collapsed into the bone both to distract the bone region, and also toallow the device to be wholly inserted into the body and/or bone. Thetelescoping body may be extended to retract the device.

The implant may be inserted quickly, but may remain in the body for anextended period (e.g., weeks, months, years). For example, the implantmay remain implanted in a bone for a month. In addition, the core of theimplant or cartridge may be removed from the outer telescoping body thatis left within the bone and replaced as a recharge or refreshedtherapeutic unit.

The implants may be any appropriate size. For example, an implantappropriate for spine may be smaller than the size of a vertebral body(e.g., between 8-50 mm in diameter)

FIGS. 1A and 1B illustrate one variation of a silver-releasing implantas described herein. FIG. 1B provides an exploded view of the implant ofFIG. 1A. In this example, the implant 100 is configured as a telescopingimplant. The body of the implant 100 is shown in the figures. The arms121 (which may also be referred to as filaments or fibers) are shownextended in FIG. 1A. In some variations the devices may includeadditional anchoring or securing features or members. For example, inFIGS. 1A and 1B, the device includes a suturable material (suture ring101) that can be secured to a tissue to further secure the device inplace. In some embodiments, extension of the arms also secures thedevice in place. In addition, the suture ring may also be impregnatedwith either silver or an antimicrobial to prevent or retard infectiononce sutured to the skin.

In FIG. 1B, the more distal body region 102 is telescoping, and may bemade of a durable, strong material (e.g., metal such as titanium) toallow the body to be extended/collapsed to distract bone or other tissueduring insertion. The distal body could also be made of a compositematerial such as carbon fiber or plastic to prevent a galvanic responsebetween the cartridge, therapeutic wires or silver. Alternatively, thebody maybe coated or formed of a material that encourages a galvanicresponse to increase the overall concentration of silver ions in theregion.

The body (including telescoping segments 101, 102, and 103) is a guidebody that also includes a passageway into which the fiber cartridge 200may be inserted. This body passageway (fiber outlet 103) may include oneor more alignment grooves 104. The alignment grove may be used to alignthe fibers so that they can be extended out of the fiber outlets 103.

As mentioned, the device may include a fiber cartridge within one ormore (typically 2 or more) arms that include a source of silver ions, anelectrode (cathode) and a connection to the power source. In FIGS. 1A-1Bthe arm shown in anti-microbial agent (e.g., silver ion) releasingfiber. This arm includes a conductor extending along the arm andconnecting proximally to the battery or other power source, and moredistally to an electrode in contact with a source of ions. Otherexamples of arms include Ag fiber, Ag plated alloys (e.g., Nitinol),coated hollow fibers (polyimide (etc)), as illustrated in FIGS. 4A and4B.

In this variation, the device includes an on-board power supply (battery300) and electronics for controlling and/or communicating the activityof the device, such as the applied current and/or voltage, and thetiming of the application of power to the arms and return electrode orelectrodes (not shown). The electronics may incorporate or executecontrol logic for controlling the power applied to release the silver.The electronics may include hardware, software and firmware (forexample, the hardware may include one or more integrated circuits forexecuting the control logic).

This example may also include a cap and/or spring 400 for holding thesilver-release driver (battery) and/or arms in position. In somevariations the battery and/or arms may be replaced in an implant afterit has been inserted into the bone. For example, just the battery 300may be replaced, or just the arms 201 may be replaced, or both may bereplaced. Thus, the body (e.g., a telescoping body) of the device mayremain in position.

FIGS. 2A and 2B show slightly enlarged views of the battery and armsportion of the device (FIG. 2A) and the implant body (the telescopingdistal end region that includes one or more openings from which the armsmay be extended. The arms 121 may engage, and be guided out of the outerguide body (shown in FIG. 2B) and be deflected into their expanded(deployed) configuration, as illustrated in FIG. 1A. The arms may bedeflected into position as the exit the ports (windows) in the guidebody 103.

FIG. 3 shows one example of an array of arms 121 that may be used. Insome variations the array of arms are individually controlled and/orconnected to the power source. In other variations each of the arms (orsub-sets of arms) are grouped together. Thus, the arms may be extended(or retracted) individually or in groups. As mentioned above, the armsinclude a silver reservoir for release of silver ions.

FIGS. 4A and 4B illustrate two variations arms that may be used. In FIG.4A the arm 401 includes a core wire 403 (electrically conductive)surrounded by a supporting metal 405 or structure. The support structuremay be nonconductive (e.g., non-conductive polymer) of it may beconductive and insulated in parts. For example, the arm may have asupport region formed of a polymer such as polyimide. In FIG. 4A, theconductor 403 may be a silver wire that is used to release ions from anexposed end region 407. In some variations the arm may include multiplerelease sites, preferably all long the length of the wire. For example,the outer region 405 may include openings or silver-ion permeableregions for release of silver. In some variations, the wire 403 may becoupled to another source of silver ions. In FIG. 4B the arm 401′includes one or more passageways 411 through which additional material(e.g., medicaments, etc.) may be passed into the body.

FIGS. 5A and 5B illustrate the device of FIGS. 1A and 1B beforeextension of the arms (seen in FIG. 5A) and after extension of the arms(seen in FIG. 5B). The arms 121 may be extended manually by advancingthe proximal end region to push the arms from the distal end openings,as described above. In some variations the implant may include a biasingmember 503 (e.g., a spring, etc.) holding the arms extended, and theproximal end of the implant may be capped. The cap and bias may beapplied after expansion of the arms by an applicator (not shown) or theymay be integral to the implant at the time of insertion/deployment.

FIG. 6 illustrates a region 603 surrounding an implanted device intowhich silver ions are released. In this example, the ions are releasedfrom the arms (at one or more electrodes on the arms) and pass into thebody in an annular region around the implant. The return electrode inthis example is on the body of the device (e.g., within or one on of thetelescoping segments of the device, or at a non-telescoping outersurface of the device.

FIG. 7 illustrates an infected region of bone 701, and FIGS. 8A-8Cillustrate the implantation and operation of another variation of animplant into this infected bone region. In this variation a telescopinginserter (which may be configured as a hollow body region of the implantitself) is inserted into the bone to from a passageway into the bone forthe device. The implant in this example includes a “reverse telescopingcannula” 801 that is inserted into the bone. For example, a relativelysmall hole may be formed in the bone into the infected region so thatthe cannula can be inserted. Inserting the cannula initially in theextended (telescoping) configuration may allow the narrower distal end(which may include one or more openings through which the arms may beextended) to be inserted into the bone. This is shown in FIG. 8A, inwhich a portion of the bone has been made transparent (appearing as acut-out) for ease of visualization. The cannula may form the outer(proximal) body of the device. Collapsing the telescoping body region ofthe cannula may distract the bone and/or anchor the device within thebone. An implant, including one or more extendable arms, may be passedinto the cannula so that the arms can be extended from the distal endand into or around an infected region of the tissue. In FIG. 8C, thetelescoping cannula (which now forms the outer portion of the implant)is collapsed down while the arms 803 are extended into the tissue. Thisdevice (including the telescoping region can be left in place to releasesilver for the desired time period (e.g., weeks, months). Alternatively,the telescoping region can be removed, leaving the rest of the implantbehind.

FIGS. 9-10C illustrate another variation of an implant configured forthe active release of silver ions. This example was configured for usein the long bone (e.g., tibia, femur, etc.) of a mammal to treatinfection. Referring to FIG. 9, a schematic of the device includes asilver-release drive (battery 901) to which a current-regulatingcircuit, including resistor 903 has been attached (by soldering in thisexample). The circuit is attached to a plurality of silver wires 905 forreleasing silver ions. A return electrode (cathode 907) is connected tothe opposite pole of the battery 901. The device may include one or moreanchors, such as the anchoring rings 913, 911 shown on the power sourceand before the release source (silver wires 905), respectively.

The return electrode (cathode 907) shown in this example is a smallplatinum wire, however, any cathode may be used. For example, in somevariations, the anchoring ring may be the return electrode.Alternatively, the cathode of the battery may be coated, or merelyexposed to form the return electrode in the tissue.

In some variations, the device does not include anchoring loops, or mayposition the anchoring loops in other positions. For example, anchoringloops may be positioned near or in communication with thesilver-releasing arms (e.g., wires).

An outer guide body (not shown) may be included over the arms (wires905) to guide the release of the wires within the bone. The guide bodymay steer the wires. In variations in which the arms have a relativelylow stiffness or ability to penetrate the bone without substantiallydeflection or deforming (as when the arms are primarily unreinforcedsilver wires), a template or passage-forming device may be used with thetreatment implant to form the passageways into which the arms (and/orthe guide body) may be inserted.

In the example shown in FIGS. 9 and 10A-D, the device includes aresistor that is calibrated so that a constant current is applied by thedevice. For example, a device having a 1.5 microamps of constant currenthas been tested in a bacterial culture, and a 15 microamp constantcurrent variation has also been tested. Both examples displayedsubstantial antimicrobial activity, including forming clearings orregions surrounding the silver-releasing material in which bacteria waseliminated or substantially eliminated. The radius of clearing wasroughly correlated with the current level. Even the very low 1.5microamp current device had a comparable effect compared to the 15microamp device, both of which produced a radius of anti-bacterialactivity that were sufficient for activity in a long bone. By includingmultiple silver-releasing elements (e.g., wires) the radius may beexpanded significantly without requiring that a higher current level beapplied, potentially increasing the battery life and effectiveness ofthe device.

A device such as the one shown in FIG. 9 was built and tested, as shownin FIGS. 10A-10C. In this example, the battery was a lithium battery(1025 Energizer™). As mentioned above, any appropriate power source maybe used, including smaller or larger batteries and external powersources. In this example, the silver wire used was a solid silver wire(99.99% silver), forming the bulk of the arm. As mentioned above, insome variations, the silver reservoir of the arm may not be a wire, butmay be a spike, coil, etc., and it may be hollow, coated, or the like.For example, the arm may be a coated Nitinol or other shape memorymaterial.

FIG. 10C illustrates the insertion of the implant into a rabbit femur.In this example, an implant such as the one shown in FIGS. 9 and 10A-Bincludes a four-strand silver wire braided array attached to a batterypower source. The self-contained implant may be scaled for use ininfected long bones, such as diabetic foot infections, where a diseasedmetatarsal may provide the implant site, or an infected jaw (e.g.,mandible). For example, the device shown in FIG. 10B has arms having alength of approximately 5 cm. In general, the device and systemsdescribed herein may be used in any size-appropriate bone, and theimplants may be sized or scaled as necessary to fit the bone.

As illustrated in FIG. 10C, the device may be implanted into a rabbithindlimb, specifically, the mid-shaft of the tibia. In thisillustration, after surgical exposure of the tibial midshaft region, anaccess hole 1005 was drilled from the outer bone layer into the centralcore of the bone (medullary cavity). A passage-forming implant devicewas then inserted to form passageways for the arms to insert through. Inthis example, the passage-forming implant includes one or morepenetrator wires that are passed along the intended wire treatment wirepath in the medullary bone and removed. The implant (including the arrayof treatment arms) was then inserted through the hole and the treatmentarms into the passageways formed by the template (passage-forming)device, and the treatment device was energized, leading to continuousrelease of silver ions into the bone. The remaining device components(e.g., the battery and catheter) were then placed into a subcutaneouspocket within the hindlimb. In this example, the wires forming the armshave been twisted to increase their stiffness/pushability. In somevariations, the arms may include another material or structure providingstiffness/pushability for implantation, even when used with a templatedevice. The arms may be placed separately (e.g., running in differentdirections along the femur or other bone regions, or wrapped around thefemur, etc.).

Another variation of a treatment implant is shown in FIGS. 12A-12D. Thisvariation illustrates a silver-releasing implant 1201 that is configuredfor use in a vertebra to treat osteomyelitis by the electricallycontrolled release of silver ions. The implant in this example is formedof Nitinol, and includes a core guide body 1203 and four extendable(curved) arms 1205 that may be deployed into the bone. The deployablearms 1205 maybe rigid and penetrating, and may be deployed, for example,into effected bony regions. In this example (as shown in FIG. 12C) thearms are shown extending from the core body region approximately 15 to 8mm (some arms are longer than others). These dimensions, including therelative dimensions of the arms and core body region, are forillustration only, and alternative dimensions may be used, includingalternative proportions. The core body in this example, has an outercylindrical region with a tapered distal end (for penetrating bone),having a diameter of approximately 3.2 mm. In some variations, thedimensions may be varied by +/−5%, 7%, 10%, 15%, 25%, 50%, 100%, 200%,etc of the values shown. In addition, the arms may extend from the corebody region in a pattern that is not uniform around the circumference ofthe implant, as shown in FIG. 12B, showing an end view of the implant.In this example, multiple arms extend out from the core guide body ononly one side of the implant (four arms are shown, all extending in theupper 140° region).

In general, when a material such as Nitinol is used, it may be desirableto coat or treat the silver to be released onto the Nitinol frame. Thisis typically done by removing the passivation coating of titanium oxideon the Nitinol, which might otherwise prevent adhesion of the silver. Toprevent exposure of the tissue to nickel, which may be undesirable, thenickel titanium alloy may be coated with an adhesion layer that may bothpassivate the nickel titanium and help adhere any silver coatings to thearms. In some variations described herein, the Nitinol may be coated orplated with an inert metal (including a conductive metal) first beforeplating the silver (and after removing any titanium oxide layer). Thus,the Nitinol structures (arms) including a silver reservoir may becovered with inert or biocompatible metal (e.g., gold, platinum, etc.)to encase the Nitinol, which is then coated with the appropriate silverlayer. In one example, a silver-plated implant was formed by a Nitinolstructure to which a gold layer was first plated followed by a silverlayer.

FIGS. 13A-13E show another variation of an implant 1300 for insertioninto a bone to treat infection. In this variation, the arms are slats orslat-like members that are inserted by sliding axially against a guidemember and/or against each other in the distal direction; as they areslid distally, the distal ends are deflected by a deflection member(e.g., a ramp or other guide region) that is present on the guide memberand on the adjacent arm(s). The arms may be collected together but ableto slide axially. In some variations, the guide member may be removableafter insertion of the arms, of it may be left in position within thebone, helping to hold the arms securely in position.

For example, in FIG. 13A, the implant includes a plurality of arms 1301,an elongate and rigid guide member 1303, and a delivery device 1305.Each of the arms 1301 is configured as an elongate member with anapproximately rectangular cross-section. The arms are all configured toslide against adjacent arms or against the guide member. In general,these arms may be configured to conform to the adjacent arms or theguide member. In the example shown in FIG. 13A, the arms have flatsurfaces that are configured to slide against adjacent flat surfaces onthe adjacent arms or the guide member. In other variations, the arms maypresent curved or rounded surfaces. In some variations, the arms mayinclude bearing surfaces (which may include additional bearingstructures between adjacent arms facilitating axial motion between thearms). The arms typically include a deflectable distal region at thedistal ends of the arms 1309, although the entire arm may bedeflectable, or just a region (e.g., a hinge region proximal to thedistal end) may be deflectable. The arms may be formed of a metal,composite, polymer, or the like (including combinations thereof). One ormore reservoirs of silver are located on each of the arms. Silverreservoir(s) may be coatings. The silver reservoir may be exposed alongall or a portion of the length, or in one or more discrete regions alongthe length. These silver-release sites may be on one or more sides ofthe arm. In FIG. 13A, each arm includes a deflection ramp 1311. Thedelivery device 1305 includes an attachment region at the distal endthat is threaded for engagement with the proximal end of the guidemember of the implant.

FIG. 13A is an exploded view of the implant. FIGS. 13B-13E illustrateone variation of a method for implanting the treatment implant shown inFIG. 13A. For example, in FIG. 13B, the elongate guide member 1303 isinserted into a bone. In this example, the bone is first pre-drilled toform a channel 1324 approximately the same size (or slightly larger)than the guide member 1303, through the cortical bone 1326 and into theintramedullary space (e.g., cancellous bone) 1322. The proximal end ofthe guide member 1303 is shown coupled to the distal end of theinsertion device 1305. In FIG. 13C, the first arm member 1331 has beenslid axially along the guide member and into the bone (beyond thecortical bone region 1326). The insertion device 1305 may include apusher element that pushes the arm axially (distally) along the guidemember. As the arm is driven distally, the distal end of the arm 1331contacts the deflection member 1313, which deflects the distal end ofthe arm away from the long axis of the guide and into the cortical bone1322. The distal end of the arm may be sufficiently sharp and/or tissuepenetrating and/or the arm may have sufficient column strength, so thatdriving the arm distally pushes the distal end of the implant along acurved pathway into the cortical bone, as shown. The proximal end of thearm may be pushed beyond the cortical bone and into the intramedullaryspace, as shown in FIG. 13C.

Thereafter, additional arms may be inserted by sliding distally, asshown in FIG. 13D. For example, each arm may be pushed over the deliverydevice (1305) using a pusher (which may be part of the device) to engageand push the proximal end of each arm. As it is slid distally, each armmay be slid along over the previous arm. The previous arm may thereforehave a gently sloped proximal end (not shown) to allow gradual loadingonto the arm by a new arm; each of the previous arms also typicallyincludes a deflection element (e.g., a ramp or protrusion) that deflectsthe distal end of the adjacent arm being loaded in a curved pathwaythrough the bone. The deflection element may be positioned at someportion of the upper surface of the adjacent arm. In some variations thearms have decreasing lengths so that they all end (when fully implanted)near about the same proximal portion of the implant; in other variationsthe proximal ends are staggered so that the later-applied arms terminatemore distally or more proximally (as shown).

FIGS. 13A-13D illustrate an implant that project (in the deliveredconfiguration) into the bone from only one side of the guide member. Insome variations, the device may be configured to project into the bonein different directions (e.g., on the bottom of the inserter in FIG.13D). The variation shown in FIGS. 14A-14C illustrates one embodiment ofthis.

Once inserted, the implant may be activated (or may be inserted in theactivated configuration) to release silver over time. For example, asilver-release driver may be coupled to each arm to drive release ofsilver from the silver reservoirs on each arm. In some variations asingle electrical drive (e.g, power source) is located within the guidemember and electrical contact is made with each silver reservoir (notshown). For example, electrical contact may be made through thedeflection members that may engage complimentary electrical contacts onthe bottom of each arm when inserted into the bone. In some variationseach arm is separately coupled to an individual silver-release driver.For example, the silver reservoir on each arm may be coupled to agalvanic reactor metal or a power source driving release of silver ions.

In some variations, the implant includes a collar or link around orbetween the arms, holding them together, even as they are axiallymovable or slideable relative to each other. For example, one or morecollars may collect the implant arms together. The collar may also holdthe guide member relative to the arms. The collar may be coupled to thesilver-release driver.

FIG. 13E illustrates one method of removing the implant of FIG. 13A. Inthis variation, the guide member may be removed from the bone leaving apassage from which each arm 1301 can be withdrawn. A removal tool (e.g.,having a grasper or engager to couple with the proximal end of each armor a plurality of arms) may be used to remove the arms and thus theimplant.

FIGS. 14A-14D show another variation of an implant having arms includinga deflection member along their length for deflection of adjacent armsas the arms are inserted axially. FIG. 14A shows an exploded view of theimplant 1400, including a plurality of arms 1401, a guide member 1403. Aportion of an inserter 1405 is also shown. FIG. 14B illustrates theimplant assembled and in a deployed configuration, with the armsextending outwards. In this variation, three sets of arms are shown,each with at least one silver reservoir for release of silver (notshown). Each set is configured so that the arms may be extended axiallyto project the arms into the bone and be stacked and slid relative toeach other so that the more radially (outer) arms are deflected by theadjacent arms. In FIG. 14C, an end view of the deployed implant shown avariation in which the arms are grouped into three sets positionedaround the perimeter of the centrally located guide member. In thisvariation, the arms are stacked atop one another. An alternativedeployed configuration is shown in FIG. 14D, in which the moreoutwardly-located arms in each set are staggered slightly along theperimeter of the guide member. This configuration may provide a slightlybroader expanse of arms in the deployed configuration. As mentionedabove, adjacent arms may be configured to slideably mate; in somevariations the configuration may allow for both the radially outwarddeflection, expanding the arms into the bone, and they may also drivethem to be offset around the circumference as shown in FIG. 14D. Forexample, the upper surface may include a track or lateral deflector.

FIGS. 15A-15C illustrate another variation of an implant 1500 similar tothat shown in FIGS. 13A and 14A; a portion of an insertion device 1509is also shown. In this example, the guide member 1507 includes aspiral-shaped deflection region 1503. Two sets of arms 1503, 1505 areincluded, each set including a silver reservoir (not shown). The firstset 1505 also includes a deflection element (e.g., ramp) along itslength. The second set of arms 1503 may be slid distally along arms ofthe first set 1505. FIG. 15B shows the implant after deployment of thefirst set 1505 of arms over the guide member 1507. FIG. 15C shows theimplant after deployment of the second set 1503 of arms over the guidemember 1507 and the first set of arms 1505.

FIGS. 16A-16C illustrate another variation of an implant having aplurality of deflectable arms that are extended from the implant by adeflection element on the guide member 1601. In this variation, theimplant includes a guide member 1601 having a deflection memberconfigured as an annular ring 1603. The arms 1605 are arranged aroundthe perimeter of the guide member in two concentric rings, as shown inthe cross-sectional view of FIG. 16C. Each arm is axially slideabledistally, relative to the guide member 1601 and/or an adjacent arm. Insome variations the implant in the undeployed (e.g., delivery)configuration has the arms pre-arranged around the central guide member1601. The arms may be collared or otherwise secured to hold them aroundthe circumference of the guide member, while allowing them to extendaxially for deployment and expansion by deflection over the deflectionelement 1603 located distally on the guide member 1601. To deploy thearms of the guide element (e.g., within the bone), the rings of arms maybe collectively or individually slid distally, axially along the lengthof the inner guide member 1601.

In any of the variations shown in FIGS. 13A, 14A, 15A and 16A, the armsand the guide member may be coupled together in the undeployedconfiguration, or they may be unassembled until they are being deployed.Also, in any of these variations any of the elements previouslydescribed (including the silver-release driver) may be included. Thesedevices may also be removed from the bone, as mentioned above.

In some variation, the device may be configured so that, upon removalfrom the bone, they automatically remove or sample a region of the bone(e.g., by “coring” a portion of the bone). Any samples removed may beexamined to determine the effect of the implant, including determiningthe presence or absence of infection. For example, in some variationsthe guide member or the arms, or some other portion of the device,includes a coring element that is oriented so as to remove a tissuesample (e.g., bone sample) when the implant or portion of the implant,is removed. FIGS. 17 and 18 illustrate variations including samplingmembers.

FIG. 17 shows a variation of an arm having a two sampling regions 1701,1703. This arm, or a plurality of similar arms, may be included in anyof the variations described above, particularly those shown in FIGS.13A, 14A, 15A and 16A. For example, the outermost (radially) arm in anyof these variations may include the sampling arm shown in FIG. 17.Withdrawing the sampling arm proximally from the bone may result inremoving of a sample (core) that is collected into the sampling regions1701, 1703.

In FIG. 18, another variation of an implant is shown in which the armshave been extended into the deployed configuration into a bone. In thisvariation, the implant includes a plurality of sampling elements 1801 onmany (if not all) of the arms and the guide member.

FIGS. 19A-19L illustrate another variation of a system including atreatment implant and a template or passage-forming device forpre-forming the passageways through the bone into which the arms of thetreatment implant will be inserted. FIG. 19A shows an exploded view ofthe system 1900, including a plurality of arms 1901, a guide member 1905and a pre-bore stylus 1907. The pre-bore stylus is the passage formingdevice that may be used with the guide member to form the passagewaysinto the bone in which the arms 1901 may be inserted.

In this example, the guide member is a rigid elongate member (althoughnon-rigid members may be used) that includes multiple guide regions,such as channels, along the device for directing the implant'ssilver-releasing arms out of the device. In the example shown in FIG.19A, these guide regions are open channels, as illustrated in thecross-sections through the guide member in FIGS. 19B and 19C. In analternative embodiment, these channels may be closed channels, as shownin alternative cross-sections 19D and 19E.

In operation, the system may be used as illustrated in FIGS. 19F-19L.Initially an insertion channel may be drilled into the bone, and theguide member inserted. The guide member may be anchored into position inthe bone. For example, the guide member may have extendable anchors (notshown). In some variations the guide member may be secured (e.g., sothat it doesn't move or rotate relative to the bone once secured) in thechannel at the proximal end, for example at the cortical bone entry siteor to the outside of the bone. In some variations, the guide member issecured within the bone by a bone cement. In some variations (similar tothat shown in FIGS. 19A-19I), the implant guide member is coupled to aninsertion tool 1925 and the insertion tool may be anchored rather than(or in addition to) the guide member 1905. The anchoring may bereleasable so that all or a portion of the implant (or the insertiontool) may be released from the bone for removal.

As illustrated in FIG. 19F, once the guide member is in position withinthe bone 1922 (past the cortical bone 1926) in a central channel 1924,channels into the bone for the placement of the arms 1924′ may be formedusing the elongate pre-bore stylus. In FIG. 19F, a single pre-borestylus may be driven along each pathway through the guide member to forma channel for each arm. Alternatively, a pre-bore stylus may havemultiple tissue (bone) penetrating members that can be guided into thebone to form the passageways. The pre-bore stylus may be abone-penetrating member having a sufficient column strength to penetratethe bone. In some variations it may be a cutting tool, includingelectrical cutting tool (e.g., electrosurgical), or a drilling tool. Thediameter of the pre-bore stylus or other template device channel-formingcomponent may be approximately the same or slightly smaller than thediameter of the arms, or in some variations, larger.

Once the channels have been formed, as illustrated in FIG. 19G, theimplant's silver-releasing arms may be inserted. The arms may beindividually inserted (as shown in FIGS. 19H-19I), or they may beinserted all together, in variations in which the arms are coupledtogether. The guide may then direct the arms as they are each sliddistally in the guide channel(s) through the channels formed by thetemplate channel-forming tool, until they are fully extended, as shownin FIG. 19I.

In some variations the implant is coupled to an inserter 1925 forinsertion. In the variation shown in FIGS. 19A-19I, the insertion deviceis shown partially illustrated and coupled to the guide member. Theinserter extends the guide channels of the guide member. In FIG. 19J,the inserter is removed from the proximal end of the implant, and theimplant may be left in position. The hole into the bone may be filled orcapped, although access may be left available to retrieve or alter theimplant later. The extended arms may help anchor the device in place,though it may be removed in whole or in part, as illustrated in FIGS.19K and 19L.

In FIG. 19K, the entire implant is removed by again coupling theproximal end of the guide member to an inserter device, or to a removaldevice that is complementary to the coupling region on the proximal endof the inserter, and drawing the implant proximally out of the bone.

Alternatively, in one variation, as shown in FIG. 19L, the individual(or a group of) the arms may be removed using an arm removal device. Inthe example shown in FIG. 19L, the guide member has been separatelyremoved, although in some variations, the guide member may be left inposition. An arm removal device may include a coupling region thatcouples to the proximal end of an arm or a group (including all) of thearms. In FIG. 19L the implant arms include a ball region at theirproximal ends, and the removal device includes a coupling member thatclamps or otherwise grasps the proximal end.

Another example of a silver-releasing implant is shown in FIGS. 20A and20B. In this example, the implant includes a guide member 2003 having aplurality of guide channels and openings 2007 at various positions alongits length. The guide member may be inserted into the bone channel 2012as described above, and the arm assembly 2001 including a plurality ofsilver-releasing arms (e.g., arms having silver depots) may be insertedinto the guide member so that the arms are guided along the length ofthe guide member and out into the bone from various positions and atvarious angles relative to the guide member, as illustrated in FIG. 20B.The proximal end of the arm assembly in this example includes a housingthat may include the silver-release driver. The housing may also beconfigured to couple to an inserter/remover (not shown), including areleasable attachment region (e.g., a threaded attachment region, asnap-fit attachment region, etc.). In some variations, the distal end ofthe housing also includes an attachment region for mating with thedistal end of the guide member.

In some variations the treatment implant includes a replaceable orrechargeable silver-release driver. For example, FIGS. 21A-21Dillustrate an system 2100 including an implant having a guide member2103, a plurality of silver-releasing arms 2101, and an endpiece 2105that includes a power supply for driving release of the silver ions. Theendpiece 2105 may include a flange rim 2097 securing it to the bonesurface, as well as an attachment site 2111 for coupling to the implant(e.g., the plurality of arms). The end piece may be secured to theimplant once it has been placed and expanded using an inserter, asmentioned above. The end piece may also include an access 2109 for abatter replacement, such as a cartridge, door, panel, etc.

FIG. 21B illustrated the variation shown in FIG. 21A after implantationinto the bone, in which the arms 2102 have been extended from the guidemember. FIG. 21C shows a cross-section through the implant,schematically illustrating the electrical connections to the arms 2102and the battery element 2121. FIG. 21D illustrates an alternativeembodiment, in which the silver release driver 2117 is insertable withinthe device (e.g., the housing 2125 of the plurality of arms).

In some variations the arms of the implant may be controllablyextendable/expandable from the implant guide member by activation of acontrol element. For example, in FIGS. 22A and 22B, one variation of asilver-releasing implant is shown in which the arms of the implant areconfigured to be extended from a guide body 2203 by rotation of aninternal extension/retraction mechanism 2205 to push (or pull whenretracting) the arms 2207 from the guide member and into the bone. Inthis example, a tool (an extension tool) 2212 may be used to turn theinternal mechanism. The internal mechanism is shown as anArchimedes-screw type mechanism that drives linear motion(forward/backward axially) of the plurality of silver-releasing arms.Other variations may also be used to control extension and/or retractionof the arms. In some variations an external tool is not required, andthe device automatically (or under remote control) extends or retractsthe arms. The arms may be fully extended from the guide member, or theymay be gradually extended to gradually expose more silver (or toreplenish depleted silver from the distal ends of the arms).

As mentioned above, in some variations the implants maybe removed inwhole or in part from the bone. In some variations, the insertion toolor device may also be used to remove the implant. In some variations aseparate or dedicated removal device may be provided. For example, FIG.23 illustrates one variation of a removal device. In general, a removaldevice may include a pair of engagement regions for individuallyengaging both the guide member of the implant and the plurality of armsof the implant. In FIG. 23, an outer engagement member 2302 isconfigured to engage the guide member at the proximal end of the guidemember, while an inner engagement member is configured to engage theplurality of arms. In this example the engagement members are clamps orjaws that controllably engage either the guide member or the pluralityof arms. Other engagement members may be used for coupling withcomplimentary coupling regions on the implant. As illustrated above, thecoupling region on the guide member and a coupling member on theplurality of arms may be a threaded region that engages a threadedmember(s) on the removal device. Threaded regions on the plurality ofarms and the guide member may be oppositely threaded.

In the exemplary device shown in FIG. 23, the inner coupling member(engagement member 2304) for coupling to the plurality of arms may beseparately controlled relative to the outer coupling member (engagementmember 2302) for coupling to the guide member, allowing the retractionand possibly removal of the arms relative to the guide member. Inoperation, the removal device may move the arms relative to the guidemember (leveraging off of the guide member) to collapse the arms.

FIGS. 24A-24E illustrate removal of another variation of asilver-releasing implant. In this example, the implant has been insertedinto the bone and a plurality of arms extended into the bone. The arms2403 extend from the distal end of the housing/guide member 2405. InFIG. 24A, the plurality of arms are coupled together in an inner member2407 that can be advanced/retracted within the guide member 2405. Theproximal end of the inner member includes a coupling region (threaded inthis example), while the proximal end of the outer member (the guidemember 2405) also includes a coupling region. In this example, a removaldevice 2424 includes an inner coupling member 2426 for coupling to theplurality of arms at the coupling region on the inner member 2407. Theremoval device also includes an outer coupling member 2428 for couplingto the guide member 2405. It should be noted that in some variations therole of the outer and inner members may be reversed (e.g., the outermember may couple to the plurality of arms and the inner member maycouple to the guide member). In some variations the two coupling membersare not arranged concentrically, but are arranged side-by-side.

In FIG. 24B the outer coupling member has been coupled to the threadedregion on the guide member. FIG. 24C shows the coupling of the innermember to the plurality of arms. The plurality of arms can then be drawnproximally, withdrawing them from the bone, as shown in FIG. 24D.Finally, in FIG. 24E the entire implant can be withdrawn. Once removed,the opening may be sealed or filled, or a new implant may be inserted.

FIGS. 25-28B illustrate different coupling regions and means forcoupling that may be used between the implant regions and the insertionor removal devices, or between regions of the implant. For example, inFIG. 25, the coupling region is a threaded region. FIGS. 26A and 26Billustrates a coupling region that is configured as afriction-engagement region in which the inner member is captured by anouter member and compression fit to secure the two ends together.Similarly, in FIGS. 27A and 27B the coupling means illustrated in FIGS.26A and 26B is shown for use to expand an inner member 2701 within asurrounding outer member 2704. The inner member 2701 may include or beused with a brace, anchor or other structure that prevents it frommoving (e.g., axially) during expansion. For example, a cylinder, rim,or lip (not shown) adjacent to the inner member may be used to brace theinner member during expansion. A mechanism such as this may be used toexpand the plurality of arms from the implant. FIGS. 28A and 28Billustrate another variation of an engagement member in which theflanges on the inner member are compressible but allowed to expand oncethey reach the engagement region in the outer member and are allowed toexpand, connecting the two regions.

FIGS. 29A-29D illustrate one variation of a silver-releasing arm. Insome variations the silver-releasing arm may be flexible, as shown inFIGS. 29A and 29B. The arm may include an inner silver depot 2901 and anouter protective cover 2903 having one or more openings 2905 from whichsilver may be released, as illustrated in FIG. 29B. In some variationsthe arms may be relatively stiff. The outer protective cover may be ametal, polymer, or the like. In some variations the arms include a shapememory material, such as a shape memory alloy, that may be pre-biasedinto a shape (curved, etc.). FIGS. 29C and 29D show enlarged andcross-sectional views, respectively, of a portion of the arm shown inFIGS. 29A-29B. In some variations the arm is not hollow orsilver-filled, as shown in FIGS. 29A-29D, but instead is coated withsilver to form the silver reservoir.

Although many of the variations described herein include a plurality ofexpandable arms, providing many of the advantages described above (suchas reaching large bone regions), in some variations it may be desirableto use a single arm, as illustrated in FIGS. 30A and 30B. In thisexample, the flexible arm shown in FIGS. 29A-29D is used as an inner armmember in conjunction with an outer member (e.g., guide) for insertionin to the bone. The inner arm 3001 (including an internal silverreservoir 3003) may be extended from the outer member 3005 to drive itinto the bone as illustrated in FIG. 30B. In operation, the inner memberis extended from the outer member after the outer member has beeninserted into the bone; the outer member is released while withdrawingit proximally, and the inner member is fed through it and into the bone.

FIGS. 31A-31C illustrate another variation of a silver-releasing armthat may be used. In this example, the arm includes an inner core ofsilver 3101 that is surrounded by an outer covering or scaffold 3105. Inthe outer covering includes openings, as seen in FIG. 31B through whichthe silver may be released. In any of the device variations describedherein the silver released from the arms may be directly released (e.g.,a silver surface may be exposed to the bone), or it may be released intoa buffer or matrix through which it may move on its way into the bone.

In one variation, the implant may include just the arms, which may beinserted into the bone, as shown in FIG. 31C. In this variation each arm3107 may include a silver release driver (such as a power source and/ora galvanic reactor metal in electrical contact with the silverreservoir).

In some variations, the implant may include a liquid reservoir fordelivery of a therapeutic material, which may include a solution ofsilver, into the bone. For example, FIG. 32A illustrates one variationof an implant having a plurality of fluid-delivery arms 3205 that arehollow and connected to a source of therapeutic fluid 2307. FIG. 32Bshows a cross-section through the fluid delivery arms of the device.

Although illustrative variations of the present invention have beendescribed above, it will be evident to one skilled in the art thatvarious changes and modifications may be made without departing from theinvention. For instance, variations of the present invention may includethe release of other (including other ionic) antimicrobial, growthhormone, other drug, or the like. In addition, the present invention mayinclude the use of the procedures described herein for therapy,repeating the procedures as often as necessary, as the amount orplacement of the implant may change over time.

What is claimed is:
 1. A bone implant to treat or prevent infection, theimplant comprising: an implant body configured to be coupled to a bone;a removable antimicrobial ion releasing member comprising anantimicrobial ion reservoir configured to be coupled to the implantbody; a galvanic reactor metal on the implant body; wherein the implantis configured to galvanically drive release of antimicrobial ions whenthe galvanic reactor metal on the implant body is in electricalcommunication with the antimicrobial ion reservoir.
 2. The implant ofclaim 1 configured as an implantable screw.
 3. The implant of claim 1,wherein the antimicrobial ion comprises silver and/or zinc.
 4. Theimplant of claim 1, wherein the implant body comprises a hollow elongatemember.
 5. The implant of claim 1, further comprising a channel withinthe implantable body configured to hold the removable antimicrobial ionreleasing member.
 6. The implant of claim 5, further comprising adeflection pathway within the channel configured to deflect theantimicrobial ion releasing member away from the implant body as theantimicrobial ion releasing member is coupled to the implant body. 7.The implant of claim 1, wherein the antimicrobial ion releasing membercomprises a shape-memory material.
 8. The implant of claim 1, whereinthe antimicrobial ion releasing member comprises a nickel titanium alloycovered by an adhesion layer and a silver coating.
 9. The implant ofclaim 1, wherein the antimicrobial ion releasing member is configured toextend from the implant body.
 10. The implant of claim 1, wherein theantimicrobial ion releasing member comprises a sharpened wire.
 11. Theimplant of claim 1, wherein the antimicrobial ion releasing membercomprises two arms configured to extend from the implant body in adeployed configuration.
 12. The implant of claim 1, wherein theantimicrobial ion releasing member is configured to release silver. 13.The implant of claim 1, wherein the antimicrobial ion reservoircomprises a silver coating.
 14. The implant of claim 1, wherein theimplant body comprises titanium.
 15. The implant of claim 1, wherein theimplant body comprises a plating from the platinum group on the periodictable.
 16. A bone implant to treat or prevent infection, the implantcomprising: an implant body having a threaded region configured to becoupled to a bone; a removable antimicrobial ion releasing membercomprising an antimicrobial ion reservoir configured to be coupled tothe implant body within a channel in the implant body; a galvanicreactor metal on the implant body; wherein the implant is configured togalvanically drive release of antimicrobial ions when the galvanicreactor metal on the implant body is in electrical communication withthe antimicrobial ion reservoir.
 17. A bone implant to treat or preventinfection, the implant comprising: an implant body having a threadedregion configured to be coupled to a bone; a removable member comprisinga galvanic reactor metal, the removable member configured to be coupledto the implant body within a channel in the implant body; anantimicrobial ion reservoir on the implant body; wherein the implant isconfigured to galvanically drive release of antimicrobial ions when thegalvanic reactor metal is in electrical communication with theantimicrobial ion reservoir.